The Expression and Distribution of IL-17 and FOXP3 in the Rectal Mucosa of HIV-Negative MSM Engaging in Condomless Receptive Anal Intercourse Open Access

Abstract

In 2017, approximately 66% of new HIV infections in United States occurred in men who have sex with men (MSM).  The majority of infections among MSM occur through exposure to the rectal mucosa, and few studies have investigated the effect of condomless receptive anal intercourse (CRAI) on the rectal mucosal immune environment.  We assessed the expression and distribution of biomarkers associated with HIV target cell populations and inflammation based on CRAI.  A cohort of 41 HIV-negative MSM engaging in CRAI and 21 HIV-negative men who never engaged in anal intercourse were recruited from the Atlanta community and enrolled in the study.  We characterized the expression, measured in optical density, of IL-17, a pro-inflammatory cytokine produced by T helper cells, and FOXP3, a transcription factor of T regulatory cells, in the rectal mucosa using standardized automated immunohistochemistry and quantitative image analysis.  The distributions of IL-17 and FOXP3 both showed trends of increased expression towards the colon lumen.  The geometric mean of the difference in IL-17 expression between the upper 40% and middle 40% of the lamina propria was 57.8 (95% CI: 40.4, 82.7, p <0.001) and the geometric mean of the difference in FOXP3 expression between the upper 40% and the middle 40% of the lamina propria was 26.9 (95% CI: 22.6, 32.0; p <0.001). The upper 40% of the lamina propria accounted for a larger proportion of expression compared to the middle 40% for both biomarkers. Modeling results did not determine any statistically significant difference in overall IL-17 or FOXP3 expression between MSM engaging in CRAI and controls, though we detected an increase in IL-17 expression in MSM after engaging in CRAI.  Our findings suggest that IL-17 and FOXP3 expression in the lamina propria of the rectal mucosa is concentrated towards the colon lumen regardless of engagement in CRAI. The localization of these regulators of inflammation towards the colon lumen and the increase in IL-17 expression in MSM after engaging in CRAI may influence the design of future preventative interventions against HIV.

Table of Contents

Background. Page 1

Methods. Page 5

The clinical cohort. Page 5

Rectal biopsy collection and biomarker quantification. Page 6

Statistical analysis. Page 8

Results. Page 11

The clinical cohort baseline characteristics. Page 11

Distribution of biomarkers through the lamina propria. Page 12

Follow-up results. Page 12

Discussion. Page 14

References. Page 17

Tables. Page 21

Table 1. Page 21

Table 2. Page 22

Figures. Page 24

Figure 1. Page 24

Figure 2. Page 25

Figure 3. Page 26

Figure 4. Page 27

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology Health Sciences, Immunology
Keyword	FOXP3 MSM HIV Immunohistochemistry Rectal Mucosa IL-17
Committee Chair / Thesis Advisor	Colleen Kelley, Emory University

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